Treating Low Resting Cardiac Output to Prevent Dementia

Introduction

Over 55 million people worldwide suffer from dementia, with prevalence expected to double over the next 20 years. In addition to the significantly decreased quality of life, dementia imposes severe financial impacts on both healthcare systems and families. In the U.S., for example, the Centers for Medicare and Medicaid (CMS) expends an average of over $26,000 annually on each of the six million Americans with dementia. Families face an equivalent level of expense for unreimbursed care giving activities. In total, annual expenditures for dementia care in the U.S. exceed $340 billion [1]. Dementia is widely understood to be the end state of a progressive process initially presenting as “normal” cognitive decline, which progresses into mild, then moderate, and finally severe, cognitive impairment, and terminates in frank dementia. Rare before age 65, over 13% of adults age 85 or older have diagnosed dementia [1].

Given the lack of effective treatments, the enormous costs of supporting patients, and our current understanding that dementia is the result of a progressive condition, CMS has been motivated to initiate a new dementia prevention strategy. As of 2023, CMS encourages Primary Care Providers (PCPs) to undertake thorough cognitive evaluations on their older adult patients with indications of cognitive aging with the goal of detecting cognitive impairment at an early, modifiable, stage. The objective is to interrupt progression as early as possible so that the risk of developing dementia is significantly reduced. The challenges associated with this new policy have been that large numbers of PCPs feel they lack a brief, accurate, clinical screening tool, nor do they have appropriate training in using existing cognitive screening tools, the time to incorporate such screening into their practice, or the confidence to diagnose the cognitive status of their patients [2]. Given that 20 or more causes of cognitive impairment have been identified, these concerns are not surprising.

The demands placed on primary healthcare providers, with respect to dementia prevention, could be greatly simplied by taking the CMS prevention strategy one step further back in the process. Rather than asking providers to learn how to identify early cognitive impairment in their older patients, healthcare providers could be equally effective in preventing a large fraction of dementia cases by addressing a much easier to diagnose issue, specifically, whether their patients present with the primary underlying cause of age-related cognitive decline.

Cognitive performance in humans typically peaks in the 4th decade of life, declines slowly through the middle-age years, and then more rapidly in the elder years [3-5]. The cause of this age-related cognitive decline is well understood, it is reduced brain blood flow. Cognitive function is strongly, and directly, dependent on cerebral perfusion, independent of age [6]. And, we know that cerebral perfusion is strongly dependent on cardiac output [7]. Resting cardiac output typically peaks in the third decade of life, then declines steadily throughout the adult years. By age 80, average resting cardiac output is only about half that observed in 20-year-olds [8,9]. These parallel, age-related, declines in resting cardiac output and cognition occur because they are directly linked through cerebral perfusion.

Fortunately, the cause of age-related decline in resting cardiac output is also well understood. Resting cardiac output is strictly dependent on venous return to the heart. In upright posture, venous return relies extensively on calf muscle pump (soleus muscle) function, but the soleus muscles are invariably atrophied in older adults due to disuse. The long lasting contractile ability (fatigue strength) of our soleus muscles is maintained through sustained postural activities such as squatting (the natural resting position of humans) and toe standing activities. However, most people undertake these activities less and less as they age. Indeed, older adults sit for an average of over 9 hours of their waking day, an activity that requires minimal soleus muscle activity. As a result, with increasing age, the fatigue strength of the soleus muscles decline, resulting in insufficient venous return, and cardiac output, throughout most of the day.

By making a point of evaluating resting cardiac output status in their older patients, a healthcare provider can contribute significantly to the goal of preventing dementia, without substantially altering routine clinical visits. It is only necessary to identify the presence of insufficient resting cardiac output, or calf muscle pump insufficiency, and then introducing an appropriate intervention. In our work, we have found that a resting cardiac index below approximately 2.6 L/min/m2 is consistently associated with below normal cognitive performance in older adults, so this should be the minimal target for resting cardiac index. While accurately assessing cardiac output has previously been a difficult and expensive procedure, new biomedical technologies are making this assessment as straightforward as obtaining an EKG or a blood pressure measurement [10]. However, even in the absence of a quantitative assessment, signs and symptoms such as the presence of lower limb edema, varicose veins, chronic fatigue, or chronically low blood pressure, can provide the PCP with assurance that their patient is experiencing chronically low resting cardiac output.

Once a healthcare provider has identified the presence of low cardiac output, the required intervention is clear for the vast majority of older individuals – the soleus muscles must be rejuvenated. This can be accomplished through simple exercises such as slow, one-legged heel raises (an older adult should be able to complete 20 or more with each foot). If exercise compliance is poor, new developments in neuro-muscular stimulation can be recommended which can passively retrain the soleus muscles [11]. Soleus muscle retraining can produce a 30%-50% increase in resting cardiac output in a 4-6 month period of time, sufficient to reverse age-related cognitive decline, and, if maintained over years, should significantly reduce the risk of dementia.

In addition, collateral age-related health complications associated with chronic lower limb fluid pooling and/or low resting cardiac output (chronic fatigue, osteoporosis, non-healing wounds, sleep apnea, drug resistant hypertension, etc.), will also be ameliorated with soleus muscle rejuvenation, improving the quality of life of patients even if significant cognitive impairment is not evident at the time of evaluation. What we commonly refer to as “normal cognitive aging” does not have to be normal, it is the result of insufficient cerebral perfusion. If we work to correct this underlying issue, we can not only reduce the burden of dementia in old age, but also the large number of health complications commonly observed in the older adult arising from chronically low resting cardiac output.

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